US20020193640A1 - Polyethylene glycol and process for producing the same - Google Patents
Polyethylene glycol and process for producing the same Download PDFInfo
- Publication number
- US20020193640A1 US20020193640A1 US10/106,219 US10621902A US2002193640A1 US 20020193640 A1 US20020193640 A1 US 20020193640A1 US 10621902 A US10621902 A US 10621902A US 2002193640 A1 US2002193640 A1 US 2002193640A1
- Authority
- US
- United States
- Prior art keywords
- glycol
- polyethylene glycol
- molecular weight
- ethylene
- diethylene glycol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 229920001223 polyethylene glycol Polymers 0.000 title claims abstract description 99
- 239000002202 Polyethylene glycol Substances 0.000 title claims abstract description 91
- 238000000034 method Methods 0.000 title claims description 15
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims abstract description 243
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims abstract description 215
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims abstract description 13
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000005977 Ethylene Substances 0.000 claims abstract description 6
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 45
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 claims description 31
- 238000012644 addition polymerization Methods 0.000 claims description 14
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 39
- 239000000047 product Substances 0.000 description 33
- 238000006243 chemical reaction Methods 0.000 description 30
- 230000000052 comparative effect Effects 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000007858 starting material Substances 0.000 description 16
- 239000011369 resultant mixture Substances 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- 230000005587 bubbling Effects 0.000 description 10
- 239000002537 cosmetic Substances 0.000 description 10
- 229910001873 dinitrogen Inorganic materials 0.000 description 9
- 239000012086 standard solution Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000000463 material Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 230000015556 catabolic process Effects 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 238000006731 degradation reaction Methods 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 239000003513 alkali Substances 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- WERYXYBDKMZEQL-UHFFFAOYSA-N butane-1,4-diol Chemical compound OCCCCO WERYXYBDKMZEQL-UHFFFAOYSA-N 0.000 description 4
- 230000000379 polymerizing effect Effects 0.000 description 4
- 239000012488 sample solution Substances 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000012159 carrier gas Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 239000008341 cosmetic lotion Substances 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- MTVMXNTVZNCVTH-UHFFFAOYSA-N ethane-1,2-diol;2-(2-hydroxyethoxy)ethanol Chemical compound OCCO.OCCOCCO MTVMXNTVZNCVTH-UHFFFAOYSA-N 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- -1 foundations Substances 0.000 description 1
- 239000005350 fused silica glass Substances 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000000976 ink Substances 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 239000000606 toothpaste Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/26—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring from cyclic ethers and other compounds
- C08G65/2603—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring from cyclic ethers and other compounds the other compounds containing oxygen
- C08G65/2606—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring from cyclic ethers and other compounds the other compounds containing oxygen containing hydroxyl groups
- C08G65/2609—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring from cyclic ethers and other compounds the other compounds containing oxygen containing hydroxyl groups containing aliphatic hydroxyl groups
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L2203/00—Applications
- C08L2203/02—Applications for biomedical use
Definitions
- This invention relates to a polyethylene glycol with low ethylene glycol and diethylene glycol contents which is to be used in fields with application to a living body such as the pharmaceutical field and the cosmetic industry, and a process for producing the same.
- Polyethylene oxide which is a material generally obtained by polymerizing ethylene oxide, has inherent characteristics of being viscous, causing no irritation, being soluble in water and having lubricating properties. Owing to these characteristics, this compound has been widely used in water base paints, paper coatings, adhesives, printing inks, surfactants and the like.
- polyethylene glycol serves as an important material in producing drugs and cosmetics in the fields with respect to a living body such as the pharmaceutical field and the cosmetic industry, since it has excellent solubility and compatibility.
- polyethylene glycol compounds called “Macrogols” having different molecular weights are listed as official drugs in the Pharmacopoeia of Japan and employed as dissolution aids and fillers in various drugs and cosmetic materials.
- Polyethylene glycol contains ethylene glycol and diethylene glycol the contents of which are specified to 0.25% (2,500 ppm) or less in the United States Pharmacopoeia etc., with respect to polyethylene glycols having a molecular weight of 1,000 or less for use in fields with application to a living body.
- x represents the average molecular weight of the polyethylene glycol.
- an object of the present invention is to provide a polyethylene glycol having an average molecular weight of from 190 to 1,050 for use in fields with application to a living body, wherein the sum of the contents of ethylene glycol and diethylene glycol is extremely low, and a process for producing the same.
- x represents the average molecular weight of the polyethylene glycol and the polyethylene glycol has an average molecular weight ranging from 190 to 1,050;
- polyethylene glycol having an average molecular weight of from 190 to 210 for use in fields with application to a living body, containing ethylene glycol and diethylene glycol in a total amount of 200 ppm or less.
- the formula [I] above is a formula whereby the sum of the ethylene glycol and diethylene glycol contents in polyethylene glycol at each molecular weight is calculated.
- the ethylene glycol and diethylene glycol contents at each molecular weight are appropriately selected depending on the requirements of an intended application. In case of use in fields with application to a living body, it is favorable from the viewpoint of toxicity that the sum of the ethylene glycol and diethylene glycol contents is 2,500 ppm or less at a molecular weight of 200. Since the sum of ethylene glycol and diethylene glycol contained in the material and the sum of ethylene glycol and diethylene glycol formed as by-products during the reaction decrease with an increase in the addition mole number of ethylene oxide, the sum of the ethylene glycol and diethylene glycol contents in the product amounts to a value calculated by multiplying by a definite decreasing ratio.
- 150 represents the molecular weight of triethylene glycol and 2,900 represents a coefficient concerning the acceptable level of the ethylene glycol and diethylene glycol contents in the material.
- (x-150)/44 means the addition mole number of ethylene oxide.
- the decreasing ratio of the sum of the ethylene glycol and diethylene glycol contents per mole of ethylene oxide added is referred to as 0.85, the upper limit of the sum of ethylene glycol and diethylene glycol contained per mole (x g) of polyethylene glycol is thus indicated.
- ethylene glycol and diethylene glycol levels are required.
- polyethylene glycol having a low molecular weight of from 190 to 210 in particular, the sum of the ethylene glycol and diethylene glycol contents is desirably 200 ppm or less.
- the present invention further provides a process for producing such a polyethylene glycol. More particularly, the present invention provides:
- the polyethylene glycol provided by the present invention is a polyethylene glycol for use in fields with application to a living body which has an average molecular weight ranging from 190 to 1,050, and the sum of the contents of ethylene glycol and diethylene glycol is less or equal to that expressed by formula [I] below.
- the polyethylene glycol provided by the present invention which is a polyethylene glycol having an average molecular weight ranging from 190 to 210 and the sum of the contents of ethylene glycol and diethylene glycol of less than or equal to that expressed by the following formula [I], still preferably 200 ppm or less, is highly useful. This is because there has been no polyethylene glycol meeting the standards as defined in the Pharmacopoeia of Japan and United States Pharmacopoeia and such a polyethylene glycol is in high demand in the market.
- x represents the average molecular weight of the polyethylene glycol.
- the upper limits at respective molecular weights calculated in accordance with the above formula [I] are as follows: 1,808 ppm in case of a polyethylene glycol having a molecular weight of 200, 833 ppm in case of a polyethylene glycol having a molecular weight of 300, 432 ppm in case of a polyethylene glycol having a molecular weight of 400, 138 ppm in case of a polyethylene glycol having a molecular weight of 600, and 19 ppm in case of a polyethylene glycol having a molecular weight of 1,000.
- Preferred values at respective molecular weights are as follows: 200 ppm in case of a polyethylene glycol having a molecular weight of 200, 150 ppm in case of a polyethylene glycol having a molecular weight of 300, 100 ppm in case of a polyethylene glycol having a molecular weight of 400, 50 ppm in case of a polyethylene glycol having a molecular weight of 600, and 15 ppm in case of a polyethylene glycol having a molecular weight of 1,000.
- a polyethylene glycol having the sum of ethylene glycol and diethylene glycol contents exceeding the level as defined by the above formula [I] is undesirable because of the excessively high content of impurities.
- the lower limit of the sum of ethylene glycol and diethylene glycol contents may be 1 ppm or more in view of the detection limit of the measurement method.
- the polyethylene glycol for use in fields with application to a living body is a physiologically useful polyethylene glycol. More particularly, it is a polyethylene glycol which is usable in products directly applied to the human body in fields with application to a living body such as drugs, cosmetics and toiletries. For example, it is useful as a medicinal base in dissolution aids, emulsifiers, dispersants, fillers, lubricating agents, etc., for injection preparations, external preparations, oral preparations and the like. Furthermore, it is useful as a cosmetic material for body cleansers such as toilet soaps, shampoos, rinses, facial cleansers and toothpastes and cosmetics such as cosmetic lotions, lotions, foundations, perfumes and lipsticks.
- body cleansers such as toilet soaps, shampoos, rinses, facial cleansers and toothpastes
- cosmetics such as cosmetic lotions, lotions, foundations, perfumes and lipsticks.
- the polyethylene glycol provided by the present invention which has small ethylene glycol and diethylene glycol contents and an average molecular weight ranging from 190 to 1,050 can be produced by addition-polymerizing ethylene oxide to triethylene glycol in the presence of an alkali catalyst such as sodium hydroxide or potassium hydroxide.
- an alkali catalyst such as sodium hydroxide or potassium hydroxide.
- the triethylene glycol for use as a starting material is not restricted in purity, it is preferable to use triethylene glycol having a purity of 99.5% or more, still preferably 99.95% or more.
- the triethylene glycol purity can be elevated by distilling, etc.
- the alkali catalyst for use in the present invention is a strongly alkaline substance such as sodium hydroxide or potassium hydroxide. It is preferably added in an amount of from 0.005 to 1.0% by weight, still preferably from about 0.01 to 0.5% by weight, based on the triethylene glycol that is supplied.
- the ethylene oxide addition-polymerization reaction is carried out preferably at a reaction temperature of from 80 to 230° C., still preferably from 120 to 180° C., and under a reaction pressure of from 0 to 1 MPa, still preferably from 0.2 to 0.6 NPa.
- ethylene glycol and diethylene glycol as by-products can be suppressed, prior to the addition-polymerization of ethylene oxide to triethylene glycol, by heating triethylene glycol in a reactor to 70 to 150° C. and bubbling nitrogen gas under reduced pressure of 0 to 0.013 MPa for 0.5 to 3 hours to thereby eliminate water from the starting materials and the catalyst.
- the ethylene glycol and diethylene glycol contents can be determined by the following method.
- sample solutions 4 g portions of samples to be measured are each precisely weighed into a 10 ml container and 5 ml of the internal standard solution and 1 ml of distilled water are precisely added thereto. After capping, the mixture is well shaken.
- WAX 52CB film thickness 1.0 ⁇ m
- Carrier gas He (helium gas).
- Injection temperature 250° C.
- Injection volume 1 ⁇ l.
- a response coefficient F N is calculated based on the peak areas obtained from the standard solution and each sample solution with the use of formula (1) below. Then, ethylene glycol and diethylene glycol are quantified using the formula (2).
- C N concentration ( ⁇ g/ml) of ethylene glycol or diethylene glycol in the standard solution
- r SI peak area of the internal standard obtained from the standard solution
- C SI concentration ( ⁇ g/ml) of the internal standard in the standard solution.
- r SN peak area of ethylene glycol or diethylene glycol obtained from the standard solution.
- C I concentration ( ⁇ g/ml) of the internal standard in the internal standard solution
- r N , r I peak areas of ethylene glycol or diethylene glycol and the internal standard obtained respectively from the sample solutions;
- W weight (g) of each target substance in the sample solution.
- the polyethylene glycol obtained by the present invention can be further processed by eliminating excessive ethylene oxide under reduced pressure and by eliminating the alkali catalyst by neutralizing the alkali catalyst with an acid such as phosphoric acid or hydrochloric acid or using an adsorbent.
- antioxidants such as dibutylhydroxyltoluene and tocopherol may be added thereto depending on the intended purpose.
- ethylene oxide was eliminated therefrom at 100C. under reduced pressure of 0.002 MPa for 1.5 hours. After cooling to 85° C., the mixture was neutralized by adding phosphoric acid and filtered to thereby give a target product (1) which was a polyethylene glycol having an average molecular weight of 202 (yield: 97%). When the obtained product was subjected to a smell test, no polyethylene glycol degradation smell was noticeable.
- Example 2 After treating as in Example 1, a target product (2) which was a polyethylene glycol having an average molecular weight of 306 was obtained (yield: 95%). When the thus obtained product was subjected to a smell test, no polyethylene glycol degradation smell was noticeable.
- Example 2 After treating as in Example 1, a target product (3) which was a polyethylene glycol having an average molecular weight of 406 was obtained (yield: 96%). When the thus obtained product was subjected to a smell test, no polyethylene glycol degradation smell was noticeable.
- Example 2 After treating as in Example 1, a target product (5) which was a polyethylene glycol having an average molecular weight of 602 was obtained (yield: 95%). When the thus obtained product was subjected to a smell test, no polyethylene glycol degradation smell was noticeable.
- the products of Examples 1, 2, 3 and 5 are polyethylene glycols respectively having molecular weights of from 190 to 210, from 285 to 315, from 380 to 420 and from 570 to 630 which were prepared using triethylene glycol as a starting material and dehydrating the triethylene glycol in a reactor before adding ethylene oxide.
- the product of Example 4 is a polyethylene glycol having a molecular weight of from 190 to 210 which was prepared using triethylene glycol as a starting material and without dehydrating the triethylene glycol before the addition polymerization with ethylene oxide.
- the ethylene glycol and diethylene glycol contents can be regulated to not more than the level defined by the above-described formula [I].
- the sum of the ethylene glycol and diethylene glycol contents can be lessened to 200 ppm or less by dehydrating the starting material before the addition polymerization with ethylene oxide.
- Comparative Examples 1 and 2 are polyethylene glycols each having a molecular weight of from 190 to 210 which were prepared using diethylene glycol as a starting material and dehydrating the diethylene glycol before the addition polymerization of ethylene oxide (Comparative Example 2) or without dehydrating (Comparative Example 1).
- Comparative Examples 3 and 4 are polyethylene glycols each having a molecular weight of from 190 to 210 which were prepared using ethylene glycol as a starting material and dehydrating the ethylene glycol before the addition polymerization of ethylene oxide (Comparative Example 4) or without dehydrating (Comparative Example 3).
- the product of Comparative Example 5 is a polyethylene glycol having a molecular weight of from 285 to 315 which was prepared using diethylene glycol as a starting material and without dehydrating the diethylene glycol before the addition polymerization of ethylene oxide.
- Comparative Examples 6 and 7 are polyethylene glycols each having a molecular weight of from 380 to 420 which were prepared using diethylene glycol as a starting material and dehydrating the diethylene glycol before the addition polymerization of ethylene oxide (Comparative Example 7) or without dehydrating (Comparative Example 6).
- the product of Comparative Example 8 is a polyethylene glycol having a molecular weight of from 570 to 630 which was prepared using diethylene glycol as a starting material and dehydrating the diethylene glycol before the addition polymerization of ethylene oxide.
- the polyethylene glycol provided by the present invention can regulate the ethylene glycol and diethylene glycol contents to an extremely low level by using triethylene glycol as a starting material and addition polymerizing with ethylene oxide.
- triethylene glycol as a starting material
- addition polymerizing with ethylene oxide By dehydrating the triethylene glycol starting material in a reactor before the addition polymerization with ethylene oxide, the ethylene glycol and diethylene glycol contents can be regulated to a further lowered level.
- the present invention provides a polyethlene glycol having the sum of the contents of ethylene glycol and diethylene glycol of less than or equal to that expressed by the following formula [I] and having an average molecular weight ranging from 190 to 1,050 adapted for use in fields with application to a living body such as medicinal preparations and cosmetics.
- a polyethylene glycol having an average molecular weight of from 190 to 210 meets the standards for ethylene glycol and diethylene glycol contents as defined in the Pharmacopoeia of Japan or United States Pharmacopoeia.
- x represents the average molecular weight of the polyethylene glycol.
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Polyethers (AREA)
- Medicinal Preparation (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/463,547 US6812367B2 (en) | 2001-03-27 | 2003-06-18 | Polyethylene glycol and process for producing the same |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JPP.2001-089455 | 2001-03-27 | ||
| JPP.2001-89455 | 2001-03-27 | ||
| JP2001089455 | 2001-03-27 | ||
| JPP.2001-357035 | 2001-11-22 | ||
| JP2001357035 | 2001-11-22 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US10/463,547 Division US6812367B2 (en) | 2001-03-27 | 2003-06-18 | Polyethylene glycol and process for producing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| US20020193640A1 true US20020193640A1 (en) | 2002-12-19 |
| US6620976B2 US6620976B2 (en) | 2003-09-16 |
Family
ID=26612151
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US10/106,219 Expired - Lifetime US6620976B2 (en) | 2001-03-27 | 2002-03-27 | Polyethylene glycol and process for producing the same |
| US10/463,547 Expired - Lifetime US6812367B2 (en) | 2001-03-27 | 2003-06-18 | Polyethylene glycol and process for producing the same |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US10/463,547 Expired - Lifetime US6812367B2 (en) | 2001-03-27 | 2003-06-18 | Polyethylene glycol and process for producing the same |
Country Status (3)
| Country | Link |
|---|---|
| US (2) | US6620976B2 (en10) |
| EP (1) | EP1245608B1 (en10) |
| DE (1) | DE60200495T2 (en10) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060069006A1 (en) * | 2004-09-24 | 2006-03-30 | Clariant Gmbh | Polyethylene glycol and alcohol ethoxylates and their preparation |
| US20130280174A1 (en) * | 2012-04-20 | 2013-10-24 | The Gillette Company | Personal care composition comprising metathesized unsaturated polyol esters |
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| ES2279374T3 (es) | 2003-06-03 | 2007-08-16 | Basf Aktiengesellschaft | Procedimiento para la elaboracion de polialquilenglicoles de alta pureza. |
| DE10325264A1 (de) * | 2003-06-03 | 2004-12-23 | Basf Ag | Hochreine Polyalkylenglykole und Verfahren zur Herstellung |
| DE10358213A1 (de) * | 2003-12-12 | 2005-07-28 | Clariant Gmbh | Polyethylenglykol und dessen Herstellung |
| US7495063B2 (en) | 2006-02-03 | 2009-02-24 | Dow Global Technologies Inc. | Reduced oligomer concentration in high purity polyalkylene glycols |
| CN102391493A (zh) * | 2006-02-03 | 2012-03-28 | 陶氏环球技术有限责任公司 | 包含减少量的低聚物的聚烷撑二醇 |
| EP1984422B1 (en) * | 2006-02-03 | 2012-06-27 | Dow Global Technologies LLC | Polyalkylene glycols comprising a reduced amount of oligomers |
| CN101605751B (zh) | 2007-01-23 | 2013-01-02 | 国际壳牌研究有限公司 | 制备烷二醇和二甲基碳酸酯的方法 |
| WO2008090108A1 (en) | 2007-01-23 | 2008-07-31 | Shell Internationale Research Maatschappij B.V. | Process for the preparation of an alkanediol and a dialkyl carbonate |
| CN101870728A (zh) | 2009-04-23 | 2010-10-27 | 派格生物医药(苏州)有限公司 | 新型Exendin变体及其缀合物 |
| WO2014089177A2 (en) | 2012-12-04 | 2014-06-12 | Massachusetts Institute Of Technology | Compounds, conjugates and compositions of epipolythiodiketopiperazines and polythiodiketopiperazines |
| US10918627B2 (en) | 2016-05-11 | 2021-02-16 | Massachusetts Institute Of Technology | Convergent and enantioselective total synthesis of Communesin analogs |
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| CN110964116A (zh) | 2018-09-26 | 2020-04-07 | 北京辅仁瑞辉生物医药研究院有限公司 | GLP1-Fc融合蛋白及其缀合物 |
| US11535634B2 (en) | 2019-06-05 | 2022-12-27 | Massachusetts Institute Of Technology | Compounds, conjugates, and compositions of epipolythiodiketopiperazines and polythiodiketopiperazines and uses thereof |
| WO2022182415A1 (en) | 2021-02-24 | 2022-09-01 | Massachusetts Institute Of Technology | Himastatin derivatives, and processes of preparation thereof, and uses thereof |
| WO2024086464A1 (en) * | 2022-10-19 | 2024-04-25 | Dow Global Technologies Llc | Liquid polyethylene glycols |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1228757B (de) * | 1962-06-28 | 1966-11-17 | Haessle Ab | Verfahren zur Herstellung eines in Wasser und Magensaft rasch zerfallenden UEberzuges auf festen Arzneiformen |
| IT987852B (it) * | 1971-05-03 | 1975-03-20 | Blendax Werke Schneider Co | Pasta dentrificia |
| US4650909A (en) * | 1984-11-28 | 1987-03-17 | Yoakum George H | Polyethylene glycol (PEG) reagent |
| JPS62227153A (ja) * | 1986-03-28 | 1987-10-06 | Oji Paper Co Ltd | Ｐｓ版用画像消去液 |
| JP2001131087A (ja) * | 1999-11-05 | 2001-05-15 | Chemo Sero Therapeut Res Inst | オイルアジュバントワクチン |
-
2002
- 2002-03-27 EP EP02007214A patent/EP1245608B1/en not_active Revoked
- 2002-03-27 DE DE60200495T patent/DE60200495T2/de not_active Revoked
- 2002-03-27 US US10/106,219 patent/US6620976B2/en not_active Expired - Lifetime
-
2003
- 2003-06-18 US US10/463,547 patent/US6812367B2/en not_active Expired - Lifetime
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060069006A1 (en) * | 2004-09-24 | 2006-03-30 | Clariant Gmbh | Polyethylene glycol and alcohol ethoxylates and their preparation |
| US20130280174A1 (en) * | 2012-04-20 | 2013-10-24 | The Gillette Company | Personal care composition comprising metathesized unsaturated polyol esters |
| CN104540493A (zh) * | 2012-04-20 | 2015-04-22 | 吉列公司 | 包含复分解化的不饱和多元醇酯的个人护理组合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| US6812367B2 (en) | 2004-11-02 |
| DE60200495T2 (de) | 2005-05-19 |
| EP1245608A1 (en) | 2002-10-02 |
| EP1245608B1 (en) | 2004-05-19 |
| US6620976B2 (en) | 2003-09-16 |
| US20030216602A1 (en) | 2003-11-20 |
| DE60200495D1 (de) | 2004-06-24 |
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